Pharmaceutical solid dosage forms, including tablets, pellets, beads, spherules and so on, are widely coated for various reasons, such as odor or taste masking, protection from moisture and light, aesthetics, delayed drug delivery, targeted drug delivery and extended drug delivery. Coated particles in multi-particulate delivery systems can exhibit many drug delivery profiles, such as taste masking, immediate release, delayed release, extended release, osmotic delivery, or any combination of the above. These drug delivery profiles can be achieved by applying one or multiple coating layer(s) (such as an initial coating of active drug materials on particles followed by an additional coating of functional polymer coating). Another method is to powder coat particles with a layer containing both active drug and functional polymeric materials on inert or active particles to achieve different release profiles.
Among the solid dosage forms, multipariculates are solid, oral dosage forms comprising several or more particles generally in the size range of 0.1 to 5 mm, preferably 0.1 to 3 mm. Multipartculate formulation with coated pellets is an important drug delivery system. It can be used to provide immediate, taste masking, extended release, delayed release and a combination of release characteristics. It is a valuable delivery system for combination drug products where multiple drugs can be incorporated in the formulation to improve patient compliance. Moreover, multiparticulates reduce the risk of dose dumping, systemic toxicity, local irritation and variation in bioavailability, as they are less dependent on gastrointestinal transit time. In contrast to monolithic devices, failure of coating will not alter the release behavior as each and every sub unit is coated and damage of single sub unit represents a small part of entire dose. The coated pellets can be dosed directly, encapsulated into capsules or compressed into tablets for ease of administration.
At present, the standard coating technology used by the pharmaceutical industry to apply coatings to particles is a liquid coating process utilizing the Wurster fluidized bed apparatus (see FIG. 1). A bottom sprayed fluidized bed with a Wurster insert was originally disclosed in U.S. Pat. No. 3,241,520 (Wruster 1966).
The Wurster fluidized bed is presently necessary for the coating of particles because the particles, due to their large specific area, tend to agglomerate while being coated in conventional pan coaters (that are used for large dosage forms coating such as tablets), whereas particles coated in a Wuster fluidized bed are well dispersed in a large air-space, allowing for the application of a uniform coating on the particle. However, there are a number of disadvantages with the use of Wurster fluidized bed technology to coat particles:
Wurster fluidized beds take up a lot space compared to conventional pan coaters because the particles in a Wurster coater need to be well dispersed in a large air-space in the fluidized bed chamber for rapid solvent removal to prevent agglomeration. Wurster fluidized beds are relatively energy inefficient because a large, constant supply of treated air (heated, moisture controlled and filtered) is required to maintain a well dispersed particle suspension during processing.
Volatile and toxic organic solvents are often required for some products e.g. for certain moisture sensitive drugs. Therefore, the costs associated with acquiring and operating Wurster fluidized beds, the facility housing the Wurster fluidized bed, and the solvent recovery/disposal equipment are very high.
Coating particles using Wurster fluidized beds is relatively slow process since the rate limited by the drying rate of the solvent of the coated particle. For instance, the coating process may take up to several days for multilayed modified release multiparticular products.
U.S. Pat. No. 7,862,848 (Zhu, Luo et al. 2011) and U.S. Pat. No. 8,161,904 (Zhu, Luo et al. 2012) discloses an electrostatic dry powder coating technique with a rotating pan coater, as shown in FIG. 2, that could be used to apply coatings to solid dosage forms such as large tablets. A drawback to this device for coating smaller sized pellets in the range 0.1 to 5 mm is that during coating, the pellets easily tend to agglomerate due to non-uniform exposure of the particles to the coating material and in the pharmaceutical industry agglomeration is a very serious problem since, if the particles agglomerate, the dissolution test of the coated pellet will fail and the product cannot be used.